The Association of Mammographic Density and Molecular Breast Cancer Subtype.

Background: Mammographic density (MD) is associated with increased breast cancer risk, yet limited data exist on an association between MD and breast cancer molecular subtypes.Methods: Women ages 18 years and older with breast cancer and available mammograms between 2003 and 2012 were enrolled in a larger study on MD. MD was classified by the Breast Imaging Reporting and Data System (BI-RADS) classification and by volumetric breast percent density (Volpara Solutions). Subtype was assigned by hormone receptor status, tumor grade, and mitotic score (MS). Subtypes included: Luminal-A (ER/PR+ and grade = 1; ER/PR+ and grade = 2 and MS = 1; ER+/PR- and grade = 1; n = 233); Luminal-B (ER+ and grade = 3 or MS = 3; ER+/PR- and grade = 2; ER/PR+ and grade = 2 and MS = 2; n = 79); Her-2-neu+ (H2P; n = 59); triple-negative (ER/PR-, Her-2-; n = 86). Precancer factors including age, race, body mass index (kg/m2), family history of breast cancer, and history of lobular carcinoma in situ were analyzed.Results: A total of 604 patients had invasive cancer; 457 had sufficient information for analysis. Women with H2P tumors were younger (P = 0.011) and had the highest volumetric percent density (P = 0.002) among subgroups. Multinomial logistic regression (LA = reference) demonstrated that although quantitative MD does not significantly differentiate between all subtypes (P = 0.123), the association between MD and H2P tumors is significant (OR = 1.06; confidence interval, 1.01-1.12). This association was not seen using BI-RADS classification in bivariable analysis but was statistically significant (P = 0.047) when controlling for other precancer factors.Conclusions: Increased MD is more strongly associated with H2P tumors when compared with LA.Impact: Delineating risk factors specific to breast cancer subtype may promote development of individualized risk prediction models and screening strategies. Cancer Epidemiol Biomarkers Prev; 26(10); 1487-92. ©2017 AACR.

Impact of Urban Neighborhood Disadvantage on Late Stage Breast Cancer Diagnosis in Virginia.

Research suggests that residents of inner-city urban neighborhoods have higher rates of late stage cancer diagnosis. Identifying urban neighborhoods with high rates of both concentrated disadvantage and late stage cancer diagnosis may assist health care providers to target screening interventions to reduce disparities. The purposes of this study were to (1) create an index to evaluate concentrated disadvantage (CD) using non-racial measures of poverty, (2) determine the impact of neighborhood CD on late stage breast cancer diagnosis in US cities, and (3) to understand the role of obesity on this relationship. We used census block group- (CBG) level poverty indicators from five Virginia cities to develop the index. Breast cancer cases of women aged 18-65 who lived in the five cities were identified from the 2000-2012 Virginia Cancer Registry. A logistic regression model with random intercept was used to evaluate the impact of disadvantage on late stage breast cancer diagnosis. CBG-level maps were developed to geographically identify neighborhoods with both high rates of CD and late breast cancer staging. Over 900 CBGs and 6000 breast cases were included. Global fit of the concentrated disadvantage model was acceptable. The effect of disadvantage on late stage was significant (OR = 1.0083, p = 0.032). Inner-city poverty impacts risk of late stage breast cancer diagnosis. Area-level obesity is highly correlated with neighborhood poverty (ρ = 0.74, p < 0.0001) but the mediating direct and indirect effects are non-significant. Intervening in these high poverty neighborhoods may help combat disparities in late stage diagnosis for urban poor and for minorities living in these underserved neighborhoods, but more study is needed to understanding the complex relationship between concentrated neighborhood poverty, obesity, and late stage diagnosis.

Surgery investigators funded through the National Institutes of Health: A rebirth.

BACKGROUND: Funding toward surgical research through the National Institutes of Health has decreased relative to other medical specialties. This study was initiated to characterize features of academically successful surgeon-scientists and departments of surgery. We hypothesized that there may be decreases in young investigators obtaining independent National Institutes of Health awards and that successful academic departments of surgery may be depending increasingly on PhD faculty. METHODS: The National Institutes of Health RePORTER database was queried for grants awarded to departments of surgery during fiscal years 2003 and 2013. Grant summaries were categorized by research methodology. Training of the principal investigator and academic position were determined through the RePORTER database and publicly available academic biographies. Institutions were ranked by number of grants funded. RESULTS: Between 2003 and 2013, total surgery grants awarded decreased by 19%. The number of National Institutes of Health-funded, clinically active surgeons (MDs) decreased 11%, while funded PhDs increased 9%; however, clinically active junior faculty have comprised an increasing proportion of funded MDs (from 20-38%). Shifts in research topics include an increasing proportion of investigators engaged in outcomes research. Among institutions ranking in the top 20 for surgical research in both 2003 and 2013 (N = 15), the ratio of MDs to PhDs was 2:1 in both fiscal years. Among institutions falling out of the top 20, this ratio was less than 1:1. CONCLUSION: There has been an expansion of outcomes-based surgical research. The most consistently successful institutions are those that actively cultivate MD researchers. Encouragingly, the number of young, independently funded surgeon-scientists in America appears to be increasing.

Sarcopenia in emergency abdominal surgery.

BACKGROUND: Sarcopenia, a loss of skeletal muscle mass associated with aging, is a practical measure of frailty and has been previously identified as a predictor of outcomes in surgical cohorts including cancer resection and elderly patients. We hypothesized that sarcopenia, as measured by preoperative computerized tomography (CT) scan, predicts mortality and morbidity in emergent laparotomy. METHODS: Institutional American College of Surgeons National Surgical Quality Improvement Program data were queried for adult patients who underwent open emergency abdominal surgery between 2008 and 2013. Patients with abdominal CT scans within 30 d before surgery were included, and cross-sectional areas of the psoas muscles at vertebral level L4 were summed, normalized by patient height, and stratified by sex. The influence of this total psoas area (TPA) on postoperative morbidity and mortality was evaluated using univariate and multivariate analysis. RESULTS: Of 781 surgeries, 593 (75.9%) had appropriate preoperative CT scans. Median patient age was 61 years old, median TPA was 1719 mm2, and median body mass index was 26.7. Univariate analysis demonstrated a significant association between TPA and total postoperative morbidity (P = 0.0133), increased length of stay (<0.0001), and 90-d mortality (P = 0.0008) but not 30-d mortality (P = 0.26). In multivariate analysis, TPA lost its significance compared to more influential predictors of mortality, including American Society of Anesthesiologists classification. CONCLUSIONS: Sarcopenia, as measured by TPA, significantly predicted mortality in univariate analysis but lost significance in multivariate analysis when factors such as American Society of Anesthesiologists score were included. Because TPA is readily available at no additional risk or cost, it is a convenient additional tool for preoperative risk assessment and counseling.

Relationship of a Second Professional Degree to Research Productivity of General Surgery Residents.

OBJECTIVE: Many general surgery residents interrupt clinical training for research pursuits or advanced degrees during dedicated research time (DRT). We hypothesize that time required to obtain a second degree during DRT decreases resident publication productivity. DESIGN, SETTING, AND PARTICIPANTS: All consecutive categorical general surgery residents at the University of Virginia in Charlottesville, VA, graduating in 2007 to 2016 were evaluated. PubMed queries identified journal publications for residents during and after DRT, limited to 1 year postgraduation. DRT varied between 1 and 3 years and was standardized by dividing publication number by DRT plus remaining clinical years and 1 postgraduation year. Median publications were compared between residents by receipt of a second degree. RESULTS: Thirty-six residents were eligible for analysis. Of these, 8 obtained a Master's in Clinical Research, 3 received Master of Public Health, and 1 completed a Doctorate of Philosophy. Publications ranged from 2 to 76 for degree residents and 1 to 36 for nondegree residents. For the 12 degree residents, median publication number per year was 3.8 (interquartile range: 2.3, 5.2) compared to 2.6 (interquartile range: 1.6, 3.5) in residents not pursuing a postdoctoral degree (p = 0.04). There was no significant difference in median number of first and second author publications by degree status. CONCLUSION: More publications per year were seen among residents earning a second degree, with a statistically significant difference between residents obtaining postdoctoral degrees during DRT compared with their counterparts. Our study demonstrates that residents pursuing a second degree are not hindered in their publication productivity despite the time investment required by the degree program. Additional research is needed to determine whether formal research training through a second degree corresponds to sustained scholarly productivity beyond residency.

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection.

BACKGROUND: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. METHODS: Five hundred eighteen patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated. Patients were stratified by obese (BMI ≥30) versus non-obese (BMI≥30) status. Descriptive comparisons were performed using Chi-square test, Fisher exact test, or Wilcoxon rank-sum tests as appropriate. Multivariable logistic regression using a priori selected variables was performed to assess the independent association between obesity and treatment failure in patients with IAI. RESULTS: Overall, 198 (38.3%) of patients were obese (BMI ≥30) versus 319 (61.7%) who were non-obese. Mean antibiotic d and total hospital d were similar between both groups. Unadjusted outcomes of surgical site infection (9.1% vs. 6.9%, p = 0.36), recurrent intra-abdominal infection (16.2% vs. 13.8, p = 0.46), death (1.0% vs. 0.9%, p = 1.0), and a composite of all complications (25.3% vs. 19.8%, p = 0.14) were also similar between both groups. After controlling for appropriate demographics, comorbidities, severity of illness, treatment group, and duration of antimicrobial therapy, obesity was not independently associated with treatment failure (c-statistic: 0.64). CONCLUSIONS: Obesity is not associated with antimicrobial treatment failure among patients with IAI. These results suggest that obesity may not independently influence the need for longer duration of antimicrobial therapy in treatment of IAI versus non-obese patients.

The prehospital and hospital costs of emergency care for frequent ED patients.

INTRODUCTION: Frequent emergency department (ED) use has been identified as a cause of ED overcrowding and increasing health care costs. Studies have examined the expense of frequent patients (FPs) to hospitals but have not added the cost Emergency Medical Services (EMS) to estimate the total cost of this pattern of care. METHODS: Data on 2012 ED visits to a rural Level I Trauma Center and public safety net hospital were collected through a deidentified patient database. Transport data and 2012 Medicare Reimbursement Schedules were used to estimate the cost of EMS transport. Health information, outcomes, and costs were compared to find differences between the FP and non-FP group. RESULTS: This study identified 1242 FPs who visited the ED 5 or more times in 2012. Frequent patients comprised 3.25% of ED patients but accounted for 17% of ED visits and 13.7% of hospital costs. Frequent patients had higher rates of chronic disease, severity scores, and mortality. Frequent patients arrived more often via ambulance and accounted for 32% of total transports at an estimated cost of $2.5-$3.2 million. Hospital costs attributable to FPs were $29.1 million, bringing the total cost of emergency care to $31.6-$32.3 million, approximately $25,000 per patient. CONCLUSIONS: This study demonstrates that the inclusion of a prehospital cost estimate adds approximately 10% to the cost of care for the FP population. In addition to improving care for a sick population of patients, programs that reduce frequent EMS and ED use have the potential to produce a favorable cost benefit to communities and health systems.

Do Polymicrobial Intra-Abdominal Infections Have Worse Outcomes than Monomicrobial Intra-Abdominal Infections?

BACKGROUND: Numerous studies have demonstrated microorganism interaction through signaling molecules, some of which are recognized by other bacterial species. This interspecies synergy can prove detrimental to the human host in polymicrobial infections. We hypothesized that polymicrobial intra-abdominal infections (IAI) have worse outcomes than monomicrobial infections. METHODS: Data from the Study to Optimize Peritoneal Infection Therapy (STOP-IT), a prospective, multicenter, randomized controlled trial, were reviewed for all occurrences of IAI having culture results available. Patients in STOP-IT had been randomized to receive four days of antibiotics vs. antibiotics until two days after clinical symptom resolution. Patients with polymicrobial and monomicrobial infections were compared by univariable analysis using the Wilcoxon rank sum, χ(2), and Fisher exact tests. RESULTS: Culture results were available for 336 of 518 patients (65%). The durations of antibiotic therapy in polymicrobial (n = 225) and monomicrobial IAI (n = 111) were equal (p = 0.78). Univariable analysis demonstrated similar demographics in the two populations. The 37 patients (11%) with inflammatory bowel disease were more likely to have polymicrobial IAI (p = 0.05). Polymicrobial infections were not associated with a higher risk of surgical site infection, recurrent IAI, or death. CONCLUSION: Contrary to our hypothesis, polymicrobial IAI do not have worse outcomes than monomicrobial infections. These results suggest polymicrobial IAI can be treated the same as monomicrobial IAI.

Does Mammographic Density have an Impact on the Margin Re-excision Rate After Breast-Conserving Surgery?

BACKGROUND: Limited and conflicting data exist on an association between mammographic density (MD) and re-excision rates after breast-conserving surgery (BCS). Additionally, the correlation of MD with resection of unnecessary margins during initial BCS is unknown. METHODS: All women with a diagnosis of breast cancer from 2003 to 2012 and enrolled in a larger study on MD were evaluated. Operative and pathology reports were reviewed to determine margin resection and involvement. Mammographic density was determined both by breast imaging-reporting and data system (BI-RADS) classification and by an automated software program (Volpara Solutions). Additional margins were deemed unnecessary if the lumpectomy specimen margin was free of invasive tumor [≥2 mm for ductal carcinoma in situ (DCIS)] or if further re-excision was needed. RESULTS: Of 655 patients, 398 (60.8%) had BCS, whereas 226 (34.5%) underwent initial mastectomy. The women with denser breasts (BI-RADS 3 or 4) underwent initial mastectomy more frequently than the women with less dense breasts (40.0 vs. 30.5%, respectively; p = 0.0118). Of the patients with BCS, 166 (41.7%) required separate re-excision. Additional margins were taken during BCS in 192 (48.2%) patients, with 151 (78.6%) proving to be unnecessary. In the bivariable analysis, the patients with denser breasts according to BI-RADS classification and volumetric density showed a trend toward requiring more frequent re-excision, but this association was not seen in the multivariable analysis. The rate of unnecessary margins did not differ by breast density. In the multivariate analysis, the re-excision rates increased with DCIS (p < 0.0003) and decreased with resection of additional margins (p = 0.0043). CONCLUSIONS: Mammographic density is not associated with an increased need for re-excision or resection of unnecessary margins at initial BCS.

Rate of lower-extremity ultrasonography in trauma patients is associated with rate of deep venous thrombosis but not pulmonary embolism.

BACKGROUND: Disparate lower-extremity ultrasonography (LUS) screening practices among trauma institutions reflecta lack of consensus regarding screening indications and whether screening improves outcomes. We hypothesized that LUS screening for deep-vein thrombosis (DVT) is not associated with a reduced incidence of pulmonary embolism (PE). METHODS: The 2012 ACS National Trauma Data Bank Research Data Set was queried to identify 442,108 patients treated at institutions reporting at least one LUS and at least one DVT. Institutions performing LUS on more than 2% of admitted patients were designated high-screening facilities and remaining institutions were designated low-screening facilities. Patient characteristics and risk factors were used to develop a logistic regression model to assess the independent associations between LUS and DVT and between LUS and PE. RESULTS: Overall, DVT and PE were reported in 0.94% and 0.37% of the study population, respectively. DVT and PE were reported more commonly in designated high-screening than low-screening facilities (DVT: 1.12% vs 0.72%, P < .0001; PE: 0.40% vs 0.33%, P = .0004). Multivariable logistic regression demonstrated that LUS was associated independently with DVT (odds ratio 1.43, confidence interval 1.34-1.53) but not PE (odds ratio 1.01, confidence interval 0.92-1.12) (c-statistic 0.86 and 0.85, respectively). Sensitivity analyses performed at various rates for designating HS facilities did not alter the significance of these relationships. CONCLUSION: LUS in trauma patients is not associated with a change in the incidence of PE. Aggressive LUS DVT screening protocols appear to detect many clinically insignificant DVTs for which subsequent therapeutic intervention may be unnecessary, and the use of these protocols should be questioned.

Recent trends in National Institutes of Health funding for surgery: 2003 to 2013.

BACKGROUND: The purpose of this study is to compare the compositions of federally funded surgical research between 2003 and 2013, and to assess differences in funding trends between surgery and other medical specialties. DATA SOURCES: The National Institutes of Health (NIH) Research Portfolio Online Reporting Tool database was queried for grants within core surgical disciplines during 2003 and 2013. Funding was categorized by award type, methodology, and discipline. Application success rates for surgery and 5 nonsurgical departments were trended over time. CONCLUSIONS: Inflation-adjusted NIH funding for surgical research decreased 19% from $270 M in 2003 to $219 M in 2013, with a shift from R-awards to U-awards. Proportional funding to outcomes research almost tripled, while translational research diminished. Nonsurgical departments have increased NIH application volume over the last 10 years; however, surgery's application volume has been stagnant. To preserve surgery's role in innovative research, new efforts are needed to incentivize an increase in application volume.

Construct validation of a cost-effective vessel ligation benchtop simulator.

OBJECTIVE: Many benchtop surgical simulators assess laparoscopic proficiency, yet few address core open surgical skills. The purpose of this study is to describe a cost-effective benchtop vessel ligation simulator and provide construct validation. DESIGN: A prospective comparison of blinded proficiency assessments among participants performing a benchtop vessel ligation simulation task. Evaluations were performed using Objective Structured Assessments of Technical Skills. SETTING: This study took place at the University of Virginia, School of Medicine: a large academic medical institution. PARTICIPANTS: The participants included fourth-year medical students participating in a focused surgical elective course (n = 16), postgraduate year 2 to 3 surgery residents (n = 6), and surgical faculty (n = 5). RESULTS: The total fixed costs of the vessel ligation simulator was $30. Flexible costs of operation were less than $0.20 per attempt. The median task-specific checklist scores among the medical students, residents, and faculty were 4.83, 7.33, and 7.67, respectively. Median global rating scores across the 3 groups were 2.29, 4.43, and 4.76, respectively. Significant proficiency differences were noted between the students and the residents/faculty for both the metrics (p < 0.001). CONCLUSIONS: A cost-effective benchtop simulator can effectively measure proficiency with basic open surgical techniques such as vessel ligation. Among the junior surgical trainees, this tool can identify learning gaps and improve operative skills in a preclinical setting.

Use of prophylactic postoperative antibiotics during surgical drain presence following mastectomy.

BACKGROUND: National guidelines recommend one dose of perioperative antibiotics for breast surgery and discourage postoperative continuation. However, reported skin and soft tissue infection (SSI) rates after mastectomy range from 1-26 %, higher than expected for clean cases. Utility of routine or selective postoperative antibiotic use for duration of drain presence following mastectomy remains uncertain. METHODS: This study included all female patients who underwent mastectomy without reconstruction at our institution between 2005 and 2012. SSI was defined using CDC criteria or clinical diagnosis of cellulitis. Information on risk factors for infection (age, body mass index [BMI], smoking status, diabetes, steroid use), prior breast cancer treatment, drain duration, and antibiotic use was abstracted from medical records. Multivariable logistic regression was used to assess the association between postoperative antibiotic use and the occurrence of SSI, adjusting for concurrent risk factors. RESULTS: Among 480 patients undergoing mastectomy without reconstruction, 425 had sufficient documentation for analysis. Of these, 268 were prescribed antibiotics (63 %) at hospital discharge. An overall SSI rate of 7.3 % was observed, with 14 % of patients without postoperative antibiotics developing SSI compared with 3.4 % with antibiotics (p < 0.0001). Factors independently associated with SSI were smoking and advancing age. Diabetes, steroid use, BMI, prior breast surgery, neoadjuvant chemotherapy, prior radiation, concomitant axillary surgery, and drain duration were not associated with increased SSI rates. CONCLUSIONS: SSI rates among patients who did and did not receive postoperative antibiotics after mastectomy were significantly different, particularly among smokers and women of advanced age. These patient subgroups may warrant special consideration for postoperative antibiotics.